PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) screening saves lives, but screening rates are low among underserved populations, particularly Latinos. The screening rate in the predominantly Latino population served by San Ysidro Health Center (SYHC, a Federally Qualified Health Center (FQHC)), is just 31%, similar to that reported for Latinos nationally, but lower than the overall national average of 65%. Previous research has demonstrated that inreach interventions at point of medical care such as patient navigation after screening referral, and outreach outside of usual medical care (such as with mailed invitations) can increase screening rates among underserved populations. However, since these have undergone limited evaluation among low income predominantly Spanish-speaking Latinos, it is unclear which approach is best, and whether implementing both approaches would be synergistic for optimizing screening rates. We hypothesize that two culturally and linguistically tailored interventions: a) an inreach strategy (IR, consisting of community health worker-delivered in clinic education regarding CRC screening and other components), and b) an outreach strategy (OS, consisting of mailed invitations to complete screening with an enclosed fecal immunochemical test (FIT) and telephone reminders) can substantially increase screening, and further, that the two interventions together will be substantially better than either alone. To test these hypotheses, we propose a randomized trial comparing usual care, IR, OS, and IR+OS for CRC screening. The proposed research is innovative because it seeks to identify the matrix of interventions required to optimize CRC screening in a Latino underserved population, is highly feasible, and has potential to be impactful for reducing cancer disparities among underserved populations, including Latinos, served at FQHCs and beyond. This project fits within the organizing framework of the partnership based on several aspects. First, it represents a hypothesis-driven research project that brings together investigators from MCC and SDSU to test strategies for addressing cancer disparities. Second, the project has a community outreach focus, as the work is entirely set within a FQHC. Third, the work increases involvement of MCC in research related to underserved populations. Fourth, the work will result in additional extramural grant applications to support cancer disparities research, particularly by new investigators who are minority scientists, such as Dr. Sheila Castaeda (Project Co-Lead). Fifth, the partnership follows the model of the Outreach Core, in which we seek to increase the impact of CC and ISUPSs collaborations by partnering our work with FQHCs.